During the last two decades, Internet-delivered cognitive behavior therapy (ICBT) has been tested in hundreds of randomized controlled trials, often with promising results. However, the control groups were often waitlisted, care-as-usual or attention control. Hence, little is known about the relative efficacy of ICBT as compared to face-to-face cognitive behavior therapy (CBT). In the present systematic review and meta-analysis, which included 1418 participants, guided ICBT for psychiatric and somatic conditions were directly compared to face-to-face CBT within the same trial. Out of the 2078 articles screened, a total of 20 studies met all inclusion criteria. Results showed a pooled effect size at post-treatment of Hedges g = .05 (95% CI, −.09 to .20), indicating that ICBT and face-to-face treatment produced equivalent overall effects. Study quality did not affect outcomes. While the overall results indicate equivalence, there have been few studies of the individual psychiatric and somatic conditions so far, and for the majority, guided ICBT has not been compared against face-to-face treatment. Thus, more research, preferably with larger sample sizes, is needed to establish the general equivalence of the two treatment formats.

Objective: Psychotherapy trials frequently generate multilevel longitudinal data with 3 levels. This type of hierarchy exists in all trials in which therapists deliver the treatment and patients are repeatedly measured. Unfortunately, researchers often ignore the possibility that therapists could differ in their performance and instead assume there is no difference between therapists in their average impact on patients' rate of change. In this article, we focus on scenarios in which therapists are fully and partially nested within treatments and investigate the consequences of ignoring even small therapist effects in longitudinal data.

Method: We first derived the factors leading to increased Type I errors for the Time x Treatment effect in a balanced study. Scenarios with an unbalanced allocation of patients to therapists and studies with missing data were then investigated in a comprehensive simulation study, in which the correct 3-level linear mixed-effects model, which modeled therapist effects using a random slope at the therapist level, was compared with a misspecified 2-level model.

Results: Type I errors were strongly influenced by several interacting factors. Estimates of the therapist-level random slope suffer from bias when there are very few therapists per treatment.

Conclusion: Researchers should account for therapist effects in the rate of change in longitudinal studies. To facilitate this, we developed an open source R package powerlmm, which makes it easy to investigate model misspecification and conduct power analysis for these designs.

Background: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety, but their efficacy relative to placebo has been questioned. We aimed to test how manipulation of verbally induced expectancies, central for placebo, influences SSRI treatment outcome and brain activity in patients with social anxiety disorder (SAD).

Methods: We did a randomized clinical trial, within an academic medical center (Uppsala, Sweden), of individuals fulfilling the DSM-IV criteria for SAD, recruited through media advertising. Participants were 18 years or older and randomized in blocks, through a computer-generated sequence by an independent party, to nine weeks of overt or covert treatment with escitalopram(20 mg daily). The overt group received correct treatment information whereas the covert group was treated deceptively with the SSRI described, by the psychiatrist, as active placebo. The treating psychiatrist was necessarily unmasked while the research staff was masked from intervention assignment. Treatment efficacy was assessed primarily with the self-rated Liebowitz Social Anxiety Scale (LSAS-SR), administered at week 0, 1, 3, 6 and 9, also yielding a dichotomous estimate of responder status (clinically significant improvement). Before and at the last week of treatment, brain activity during an emotional face-matching task was assessed with functional magnetic resonance imaging (fMRI) and during fMRI sessions, anticipatory speech anxiety was also assessed with the Spielberger State-Trait Anxiety Inventory - State version (STAI-S). Analyses included all randomized patients with outcome data at posttreatment. This study is registered at ISRCTN, number 98890605.

Interpretation: The clinical and neural effects of escitalopram were markedly influenced by verbal suggestions. This points to a pronounced placebo component in SSRI-treatment of SAD and favors a biopsychosocial over a biomedical explanatory model for SSRI efficacy.